This paper is a report of a study conducted in 2004 on the determinants of attitudes towards hormone replacement therapy in the aftermath of the report on the findings of the Women's Health ...Initiative study. The unexpected findings of the Women's Health Initiative study, published in July 2002, showed that the risk of using combined hormones exceeded their benefits. This complicated women's decision-making about hormone use and made it important to study the determinants of their attitudes to hormone therapy, as these are likely to influence their behaviour. A cross-sectional design was conducted with a sample of 561 women drawn from the National Registry of Iceland. A self-administered questionnaire, measuring attitudes towards hormone replacement therapy, attitudes towards menopause, extent and source of menopausal education, symptom experience, health and lifestyle and knowledge about the findings of the Women's Health Initiative, was used. The overall response rate was 56%. Attitudes to hormone replacement therapy were compared using anova, t-tests and correlations. Participants generally had positive attitudes. Knowledge about the Women's Health Initiative study was not associated with more negative attitudes. However, receiving the information from and discussing it with a doctor were associated with more positive attitudes. Positive attitudes towards hormone therapy were also associated with higher age, time since last menstrual period and current use of hormone replacement therapy. Negative attitudes were associated with use of natural remedies and receiving information from or discussing hormone therapy with family or friends. Research is needed to identify the dynamics of the medical interview, and the nature of input from friends, spouse and other family members. The content of these messages may be different and conflicting, for example, between doctors and family members. The nature of this conflict and conflicts of interests need to be identified in order to inform women's decision-making. In addition, action needs to be taken in order to strengthen the advisory role of nurses.
• Is PISA 2012 relevant to mathematics education in Norway and Sweden?
• In what ways are the different leadership styles among principals in the Nordic countries related to teachers’ attitudes and ...behaviours and students achievements?
• What are the associations between professional development, job satisfaction and self-efficacy?
• Can collegial work and school leader feedback improve teachers’ self-efficacy in Nordic classrooms?
• What characterizes high-performing students in mathematics within the Nordic countries?
• Are international large-scale educational assessments elephants arriving at the gates of our national educational system?
These are some of the questions that are discussed in this collection of articles. The issues are based on the results of the OECD studies PISA and TALIS. The articles aim to provide input for policy discussions and to further policy development within the Nordic countries. Therefore, the main target groups are educational ministers and policymakers at all levels. These analyses will also provide input to the joint Nordic initiatives on educational development.
It has been suggested that mental habits may underpin a heightened disposition to engage in rumination in response to negative mood. The aim of the current study was to assess the role of habit in ...the dynamic interplay between affect and ruminative thinking in the flow of daily life experiences. Using mobile ecological momentary assessment, 97 participants recorded affect and rumination ten times daily over six days, after completing measures of trait ruminative brooding and habitual characteristics of negative thinking (e.g. automaticity, lack of conscious awareness, intent and control). Momentary fluctuations in negative (increased) and positive (decreased) affect was prospectively associated with greater rumination-levels at the next sampling occasion. The degree to which affect triggered a subsequent ruminative response was moderated by habitual characteristics of negative thinking in a theoretically consistent way. Stronger temporal pairing of negative affect and rumination was also associated with greater emotional inertia but less carry-over of rumination from one moment to the next. Depression vulnerability may be in the form of rumination being habitually triggered in response to momentary fluctuations in affect, with deleterious effect on mood. The findings may have clinical implications, as targeting the habitual nature of rumination might help reduce depression vulnerability.
•The role of habit in rumination was studied using ecological momentary assessment.•Daily fluctuations in negative and positive affect predicted subsequent rumination.•Affect triggered greater rumination when associated with habitual characteristics.•Mood-linked rumination was associated with greater emotional inertia.
Gallstones are responsible for one of the most common diseases in the Western world and are commonly treated with cholecystectomy. We perform a meta-analysis of two genome-wide association studies of ...gallstone disease in Iceland and the UK, totaling 27,174 cases and 736,838 controls, uncovering 21 novel gallstone-associated variants at 20 loci. Two distinct low frequency missense variants in SLC10A2, encoding the apical sodium-dependent bile acid transporter (ASBT), associate with an increased risk of gallstone disease (Pro290Ser: OR = 1.36 1.25-1.49, P = 2.1 × 10
, MAF = 1%; Val98Ile: OR = 1.15 1.10-1.20, P = 1.8 × 10
, MAF = 4%). We demonstrate that lower bile acid transport by ASBT is accompanied by greater risk of gallstone disease and highlight the role of the intestinal compartment of the enterohepatic circulation of bile acids in gallstone disease susceptibility. Additionally, two low frequency missense variants in SERPINA1 and HNF4A and 17 common variants represent novel associations with gallstone disease.
Long-read sequencing (LRS) promises to improve the characterization of structural variants (SVs). We generated LRS data from 3,622 Icelanders and identified a median of 22,636 SVs per individual (a ...median of 13,353 insertions and 9,474 deletions). We discovered a set of 133,886 reliably genotyped SV alleles and imputed them into 166,281 individuals to explore their effects on diseases and other traits. We discovered an association of a rare deletion in PCSK9 with lower low-density lipoprotein (LDL) cholesterol levels, compared to the population average. We also discovered an association of a multiallelic SV in ACAN with height; we found 11 alleles that differed in the number of a 57-bp-motif repeat and observed a linear relationship between the number of repeats carried and height. These results show that SVs can be accurately characterized at the population scale using LRS data in a genome-wide non-targeted approach and demonstrate how SVs impact phenotypes.
Lipoprotein(a) Lp(a) is a causal risk factor for cardiovascular diseases that has no established therapy. The attribute of Lp(a) that affects cardiovascular risk is not established. Low levels of ...Lp(a) have been associated with type 2 diabetes (T2D).
This study investigated whether cardiovascular risk is conferred by Lp(a) molar concentration or apolipoprotein(a) apo(a) size, and whether the relationship between Lp(a) and T2D risk is causal.
This was a case-control study of 143,087 Icelanders with genetic information, including 17,715 with coronary artery disease (CAD) and 8,734 with T2D. This study used measured and genetically imputed Lp(a) molar concentration, kringle IV type 2 (KIV-2) repeats (which determine apo(a) size), and a splice variant in LPA associated with small apo(a) but low Lp(a) molar concentration to disentangle the relationship between Lp(a) and cardiovascular risk. Loss-of-function homozygotes and other subjects genetically predicted to have low Lp(a) levels were evaluated to assess the relationship between Lp(a) and T2D.
Lp(a) molar concentration was associated dose-dependently with CAD risk, peripheral artery disease, aortic valve stenosis, heart failure, and lifespan. Lp(a) molar concentration fully explained the Lp(a) association with CAD, and there was no residual association with apo(a) size. Homozygous carriers of loss-of-function mutations had little or no Lp(a) and increased the risk of T2D.
Molar concentration is the attribute of Lp(a) that affects risk of cardiovascular diseases. Low Lp(a) concentration (bottom 10%) increases T2D risk. Pharmacologic reduction of Lp(a) concentration in the 20% of individuals with the greatest concentration down to the population median is predicted to decrease CAD risk without increasing T2D risk.
Display omitted
Creatine kinase (CK) and lactate dehydrogenase (LDH) are widely used markers of tissue damage. To search for sequence variants influencing serum levels of CK and LDH, 28.3 million sequence variants ...identified through whole-genome sequencing of 2,636 Icelanders were imputed into 63,159 and 98,585 people with CK and LDH measurements, respectively. Here we describe 13 variants associating with serum CK and 16 with LDH levels, including four that associate with both. Among those, 15 are non-synonymous variants and 12 have a minor allele frequency below 5%. We report sequence variants in genes encoding the enzymes being measured (CKM and LDHA), as well as in genes linked to muscular (ANO5) and immune/inflammatory function (CD163/CD163L1, CSF1, CFH, HLA-DQB1, LILRB5, NINJ1 and STAB1). A number of the genes are linked to the mononuclear/phagocyte system and clearance of enzymes from the serum. This highlights the variety in the sources of normal diversity in serum levels of enzymes.
Uterine leiomyomas are common benign tumors of the myometrium. We performed a meta-analysis of two genome-wide association studies of leiomyoma in European women (16,595 cases and 523,330 controls), ...uncovering 21 variants at 16 loci that associate with the disease. Five variants were previously reported to confer risk of various malignant or benign tumors (rs78378222 in TP53, rs10069690 in TERT, rs1800057 and rs1801516 in ATM, and rs7907606 at OBFC1) and four signals are located at established risk loci for hormone-related traits (endometriosis and breast cancer) at 1q36.12 (CDC42/WNT4), 2p25.1 (GREB1), 20p12.3 (MCM8), and 6q26.2 (SYNE1/ESR1). Polygenic score for leiomyoma, computed using UKB data, is significantly correlated with risk of cancer in the Icelandic population. Functional annotation suggests that the non-coding risk variants affect multiple genes, including ESR1. Our results provide insights into the genetic background of leiomyoma that are shared by other benign and malignant tumors and highlight the role of hormones in leiomyoma growth.
Abstract
Aims
To explore whether variability in dietary cholesterol and phytosterol absorption impacts the risk of coronary artery disease (CAD) using as instruments sequence variants in the ABCG5/8 ...genes, key regulators of intestinal absorption of dietary sterols.
Methods and results
We examined the effects of ABCG5/8 variants on non-high-density lipoprotein (non-HDL) cholesterol (N up to 610 532) and phytosterol levels (N = 3039) and the risk of CAD in Iceland, Denmark, and the UK Biobank (105 490 cases and 844 025 controls). We used genetic scores for non-HDL cholesterol to determine whether ABCG5/8 variants confer greater risk of CAD than predicted by their effect on non-HDL cholesterol. We identified nine rare ABCG5/8 coding variants with substantial impact on non-HDL cholesterol. Carriers have elevated phytosterol levels and are at increased risk of CAD. Consistent with impact on ABCG5/8 transporter function in hepatocytes, eight rare ABCG5/8 variants associate with gallstones. A genetic score of ABCG5/8 variants predicting 1 mmol/L increase in non-HDL cholesterol associates with two-fold increase in CAD risk odds ratio (OR) = 2.01, 95% confidence interval (CI) 1.75–2.31, P = 9.8 × 10−23 compared with a 54% increase in CAD risk (OR = 1.54, 95% CI 1.49–1.59, P = 1.1 × 10−154) associated with a score of other non-HDL cholesterol variants predicting the same increase in non-HDL cholesterol (P for difference in effects = 2.4 × 10−4).
Conclusions
Genetic variation in cholesterol absorption affects levels of circulating non-HDL cholesterol and risk of CAD. Our results indicate that both dietary cholesterol and phytosterols contribute directly to atherogenesis.
PDF
